Background Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2005412

Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington.

Background Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is o...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2016638?articleTools=true

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.

Importance Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. Objective To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19–associated ARDS. Design, Setting, and Participants Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Interventions Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). Main Outcomes and Measures The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. Results A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38;P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, −1.16; 95% CI, −1.94 to −0.38;P= .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. Conclusions and Relevance Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days. Trial Registration ClinicalTrials.gov Identifier:NCT04327401

/pdf/effect-of-dexamethasone-on-days-alive-and-ventilator-free-in-1z6emrvlca.pdf

Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.

Background Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2019014

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.

/pdf/extrafollicular-b-cell-responses-correlate-with-neutralizing-uvy9mgl3qb.pdf

Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19.

The REDCap consortium: Building an international community of software platform partners.

Introduction The use of online platforms for pediatric healthcare research is timely, given the current pandemic. These platforms facilitate trial efficiency integration including electronic consent, randomization, collection of patient/family survey data, delivery of an intervention, and basic data analysis. Methods We created an online digital platform for a multicenter study that delivered an intervention for sleep disorders to parents of children with autism spectrum disorder (ASD). An advisory parent group provided input. Participants were randomized to receive either a sleep education pamphlet only or the sleep education pamphlet plus three quick-tips sheets and two videos that reinforced the material in the pamphlet (multimedia materials). Three measures - Family Inventory of Sleep Habits (FISH), Children's Sleep Habits Questionnaire modified for ASD (CSHQ-ASD), and Parenting Sense of Competence (PSOC) - were completed before and after 12 weeks of sleep education. Results Enrollment exceeded recruitment goals. Trial efficiency was improved, especially in data entry and automatic notification of participants related to survey completion. Most families commented favorably on the study. While study measures did not improve with treatment in either group (pamphlet or multimedia materials), parents reporting an improvement of ≥3 points in the FISH score showed a significantly improved change in the total CSHQ (P = 0.038). Conclusion Our study demonstrates the feasibility of using online research delivery platforms to support studies in ASD, and more broadly, pediatric clinical and translational research. Online platforms may increase participant inclusion in enrollment and increase convenience and safety for participants and study personnel.

/pdf/a-redcap-based-model-for-online-interventional-research-13trzn5uvh.pdf

Lindsay O'Neal

Papers

The REDCap consortium: Building an international community of software platform partners.

A REDCap-based model for online interventional research: Parent sleep education in autism